Clostridium difficile (C. difficile) is a gram-positive spore-forming, anaerobic bacteria. Pathological effects of C. difficile are mediated by the secreted toxins A and B, which cause colonic mucosal injury and inflammation. Although C. difficile infection (CDI) is asymptomatic in some patients, CDI may result in acute diarrhea and colitis, and in severe cases can lead to pseudomembranous colitis and toxic megacolon. C. difficile is a clinically important cause of nosocomial diarrhea and colitis in hospitalized patients receiving drugs that alter normal gut flora, and CDI is increasingly reported in the community. Risk factors for symptomatic C. difficile infection include antibiotic treatment, advanced age, underlying illness, and hospitalization or residence in a long-term care facility.
Early phase clinical trials have been conducted to evaluate the safety and immunogenicity of versions of C. difficile toxoid vaccines. In healthy adult (18-55 years old) and elderly (≧65 years old) volunteers, an earlier evaluated C. difficile vaccine comprising toxoid A and B proved safe and elicited an immune response to both toxin A and toxin B (Greenberg, et al. Vaccine 30: 2245-2249 (2012); Foglia, et al. Vaccine, 30: 4307-4309 (2012)). The maximal dose in such studies was 50 μg and the toxin A to toxin B ratio 3:1. The candidate vaccine was administered on days 0, 28 and 56. Seroconversion to toxin A was higher than toxin B after multiple doses in both the healthy adult and elderly volunteer groups and a more rapid decline in the antibody response in elderly subjects as compared to the younger group was observed. Those of ordinary skill in the art recognize this as a significant problem as the elderly are often immunocomprised. The need for a C. difficile vaccine for use in adults at risk of a symptomatic C. difficile infection continues, especially in the elderly.